First-Line Anti-Tuberculosis Drug Susceptibility Patterns of Mycobacterium tuberculosis Complex Strains Responsible for New Cases of Human Pulmonary Tuberculosis in Kisumu County, Western Kenya

Background: Tuberculosis (TB) remains a major cause of morbidity and mortality worldwide, drug-resistant tuberculosis being a major public health problem. The emergence and spread of multidrug resistant (MDR) Mycobacterium tuberculosis complex (MTBC) strains poses significant challenges to disease control. Continued surveillance of drug susceptibility helps determining proper treatment regimen. The effectiveness of a standard anti-tuberculosis (TB) treatment regimen correlates with in vitro drug susceptibility pattern of the infecting tubercle bacilli. The results of the drug susceptibility tests help select a proper treatment regimen or modify treatment regimen for a better management of patients and surveillance and timely control of the spread of the drug resistant TB in the community. Treatment of drug resistant TB is costly, and the outcomes, including survivorship, can be poor. As the result, the drug susceptibility test has become more important than ever. Objective: This study aimed to investigate the patterns of first line anti-tuberculosis drug-susceptibility against Mycobacterium tuberculosis complex isolates from new cases of pulmonary TB patients in Kisumu County, Western Kenya. Method: This was a cross sectional study which included a total of 290 isolates from pulmonary TB patients in JOOTRH and Kisumu County Hospital between February and August 2016. The MTBC isolates identified were M. tuberculosis, M. africanum, and M. bovis. Drug susceptibility test was performed on the 283 M. tuberculosis, 5 M. africanum and 2 M. bovis isolates by BD BACTEC MGIT 960 SIRE and PZA DST system using five first-line anti-TB drugs: Isoniazid, Rifampicin, Streptomycin, Ethambutol and Pyrazinamide. Results: M. tuberculosis was highly sensitive to all the anti-TB drugs; Streptomycin(S) 96.8%, Isoniazid (H) 89.8%, Rifampin(R) 98.2%, Ethambutol (E) 94.4%, Pyrazinamide (PZA) 89.8%. M. bovis TB species was 100% sensitive to all drug except Pyrazinamide where there was 100% resistance. M. africanum varied in its sensitivity to anti-TB drugs; Streptomycin 80%, Isoniazid 60%), Pyrazinamide 4 (80%). Resistance was Streptomycin 20%, Isoniazid 40%, and Pyrazinamide 20%. M. africanum was neither resistant to Rifampin(R) nor Ethambutol (E). A total of 20.8% of M. tuberculosis strains showed resistance to at least one drug tested, while 79.2% were sensitive. 16.3% were resistant to one drug (mono resistance), 2.1% to two drugs (double resistance), 0.7% to three drugs (triple resistance), 0.4% to four drugs (quadruples) and 1.4% to five drugs (pentagon-resistance). Two isolates of M. bovis were resistant to one drug. Two isolates of M. africanum were resistance, one case to one drug and another one case to three drugs. Conclusion: This study showed high level of resistance in M. tuberculosis isolates warranting proper use of anti-TB drugs in Kisumu County. Keywords: Tuberculosis, M. tuberculosis complex, Multi Drug Resistanc

Molecular Identity of Mycobacteria Isolates in New Cases of Pulmonary Tuberculosis Patients in Kisumu County, Western Kenya

Background: Pulmonary tuberculosis (TB) remains one of the most challenging diseases to control in the world today and it has become a major global health problem especially in immunocompromised people such as HIV/AIDS. The problem is compounded by the emergence of non-tuberculous mycobacteria (NTM) of which its treatment is not directly analogous to that of MTB. Objective: This study determined the identity of Mycobacteria isolates in new cases of human pulmonary TB patients. Methods: It was a cross-sectional study that involved 316 confirmed new cases of pulmonary TB attending JOOTRH and Kisumu County Hospital. Sputa specimen was cultured in MGIT liquid culture medium. The isolates were identified to species level using GenoType® Mycobacterium CM/AS and MTBC Assay from Hain Lifescience Germany. Results. Of the 316 culture positive isolates, 91.8% were identified as MTBC and 8.2% were NTM species. Of the 290 MTBC, three different species were identified, 97.6% were M. tuberculosis, 1.7% were M. africanum and 0.7% were M. bovis. The Fisher’s exact test was used to assess the associations between patient characteristics and MTBC species identified showed that age category of patients less than 35 years and above 35 years were statistically significant with MTBC species (p=0.020). While sex was not statistically significant with MTBC species (p=0.696). Four different NTM species were identified as 61.5% M. intracellulare, 19.2% M. abscessus, 11.5% M. kansasii and 7.7% M. fortuitum. The Fisher’s exact test done to assess the associations between patient characteristics and NTM species was identified. Age category (p=0.608) and sex (p=0.182) of patients was not statistically significant to NTM species. Conclusion: There is a need for routine speciation among members of the MTBC and NTM as it is an important prerequisite for the proper management of patients with mycobacterial infections. Keywords: Mycobacterium tuberculosis complex, Non tuberculous mycobacteria, Tuberculosi

Benefits of enhanced infection prophylaxis at antiretroviral therapy initiation by cryptococcal antigen status

OBJECTIVES: To assess baseline prevalence of cryptococcal antigen (CrAg) positivity; and its contribution to reductions in all-cause mortality, deaths from cryptococcus and unknown causes, and new cryptococcal disease in the REALITY trial. DESIGN: Retrospective CrAg testing of baseline and week-4 plasma samples in all 1805 African adults/children with CD4(+) cell count less than 100 cells/μl starting antiretroviral therapy who were randomized to receive 12-week enhanced-prophylaxis (fluconazole 100 mg/day, azithromycin, isoniazid, cotrimoxazole) vs. standard-prophylaxis (cotrimoxazole). METHODS: Proportional hazards models were used to estimate the relative impact of enhanced-prophylaxis vs. standard-cotrimoxazole on all, cryptococcal and unknown deaths, and new cryptococcal disease, through 24 weeks, by baseline CrAg positivity. RESULTS: Excluding 24 (1.4%) participants with active/prior cryptococcal disease at enrolment (all treated for cryptococcal disease), 133/1781 (7.5%) participants were CrAg-positive. By 24 weeks, 105 standard-cotrimoxazole vs. 78 enhanced-prophylaxis participants died. Of nine standard-cotrimoxazole and three enhanced-prophylaxis cryptococcal deaths, seven and two, respectively, were CrAg-positive at baseline. Among deaths of unknown cause, only 1/46 standard-cotrimoxazole and 1/28 enhanced-prophylaxis were CrAg-positive at baseline. There was no evidence that relative reductions in new cryptococcal disease associated with enhanced-prophylaxis varied between baseline CrAg-positives [hazard-ratio =0.36 (95% confidence interval 0.13−0.98), incidence 19.5 vs. 56.5/100 person-years] and CrAg-negatives [hazardratio =0.33 (0.03−3.14), incidence 0.3 vs. 0.9/100 person-years; P(heterogeneity) =0.95]; nor for all deaths, cryptococcal deaths or unknown deaths (P(heterogeneity) > 0.3). CONCLUSION: Relative reductions in cryptococcal disease/death did not depend on CrAg status. Deaths of unknown cause were unlikely to be cryptococcus-related; plausibly azithromycin contributed to their reduction. Findings support including 100 mg fluconazole in an enhanced-prophylaxis package at antiretroviral therapy initiation where CrAg screening is unavailable/impractical